Until recent years, each type of human phagocytic leukocyte (monocytes, macrophages, neutrophils, eosinophils) had been considered to contain a single type; of IgG Fc receptor (FcGammaR). Newer studies, by our lab and othrs, have demonstrated the existence of three classes of FcGammaR (40 Kd, 55-68 Kd, and 72 Kd) on human blood cells, each identified by a monoclonal antibody. Current evidence indicates that a given type of leukocyte may express 1, 2, or (in the case of tissue macrophages) all three classes of FcGammaR. There are important functional differences among these classes of FcGammaR; e.g., the 72 Kd receptor has a high affinity for monomeric IgG whereas the 40 Kd and 55-68 Kd receptor have a lower affinity for monomeric IgG but bind multivalent IgG complexes even in the presence of excess monomer. Differences among the 3 FcGammaR receptors in specificity for subclasses of IgG may also exist. These functional differences are undoubtedly important in immune complex clearance and host defense mechanisms. My work will concentrate on the newly described 40 Kd FcGammaR. The 40 Kd FcGammaR on human monocytes, granulocytes, and platelets (but not on B lymphocytes) is rcognized by our monoclonal antibody IV.3. We will use isoelectric focusing gels and peptide mapping to see if the B cell receptor is closely related to the receptor recognized by IV.3. The 40 Kd receptors on monocytes from different individuals vary in their ability to bind mouse IGG1. We will look for structural heterogeneity of the 40 Kd FcGammaR on monocytes as evidence of allotypic variation. As a prelude to cloning the gene for the 40 Kd FcGammaR antibodies including a panel of monoclonals against different epitopes and a monospecific rabbit antiserum, 2) isolate transfected L cells expressing the 40 Kd FcGammaR, and 3) isolate purified tryptic peptides to obtain a partial amino acid sequence. There is data from the studies of another laboratory suggesting that some FcGammaRs are intimately associted with phospholipase AE2 activity. We will evaluate the association of PLA2 activity and the 40 Kd FcGammaR. We will also see if the 40 Kd FcGammaR can trigger ADCC and phagocytosis.